Comparing the efficacy of angiotensin receptor-neprilysin inhibitor and enalapril in acute anterior STEMI patients after primary percutaneous coronary intervention: a prospective randomized trial.

Background: For patients with heart failure (HF), the effect of angiotensin receptor-neprilysin inhibitors (ARNIs, sacubitril/valsartan) on cardiac remodeling has been found to be superior to angiotensin-converting enzyme inhibitors (ACEI). However, little data have described the impact of early-initiation ARNI in patients with acute anterior ST-segment elevation myocardial infarction (STEMI). Methods: In this prospective, randomized, double-blind, parallel-group trial, we enrolled 131 anterior STEMI patients who were treated with primary percutaneous coronary intervention (PCI) between February 2019 and December 2019. All patients received standard STEMI management and were divided into 2 groups (ARNI/enalapril). Primary efficacy outcomes were the between-group difference in change (from baseline to 4-, 12-, and 24-week) in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration, left ventricular ejection fraction (LVEF), and left ventricular end-systolic volumes and end-diastolic volumes (LVESV and LVEDV). Secondary outcomes were determined by a composite of death, reinfarction, outpatient HF or HF hospitalization, malignant arrhythmia, and stroke. Safety outcomes included worsening renal function, hypotension, hyperkalemia, angioedema and cough. Results: We found that NT-proBNP concentration decreased more in the ARNI group than in the enalapril group [4 weeks: ratio of ARNI vs. enalapril 0.36, 95% confidence interval (CI): 0.24 to 0.52, P<0.001; 12 weeks: 0.54, 95% CI: 0.35 to 0.79, P<0.001; 24 weeks: 0.53, 95% CI: 0.32 to 0.83, P<0.001). When compared to the enalapril group, the ARNI group patients had a significant reduction in LVEDV (P<0.001) and LVESV (P<0.001), and an improvement in LVEF (P=0.011) at 24 weeks. Secondary outcomes occurred in 13 participants (20.3%) in the ARNI group and 22 participants (34.4%) in the enalapril group [hazard ratio (HR), 0.56; 95% CI: 0.28 to 1.12; P=0.102]. The incidence of outpatient HF or HF hospitalization in the ARNI group was significantly lower than that in the enalapril group (HR, 0.36; 95% CI: 0.14 to 0.94; P=0.037). There were no significant differences in the safety between the 2 groups. Conclusions: For patients with acute anterior STEMI undergoing primary PCI, early initiation of ARNI provided significant clinical benefits. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100042944) registered on February 1, 2021.